PB2041: EVALUATION OF THE PROGNOSTIC VALUE OF THROMBOPHILIA MARKERS IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS
Authors: T. Makarik, K. Sabirov, E. Kitsenko, S. Treglazova, E. Stepanova, I. Fevraleva, S. Kulikov, A. Sudarikov
Journal: HemaSphere (2022)

Background: The clinical course of myeloproliferative neoplasms (MPN) is often complicated by impaired microcirculation, arterial and venous thrombosis. According to the literature, common for MPNs JAK2 gene mutations may contribute to the development of venous thrombosis. Even in the absence of overt MPN, a significant proportion of patients with recurrent cerebral and/or portal vein thrombosis carry the JAK2 V617F mutation. It is known that hereditary thrombophilic conditions, such as congenital deficiency of anticoagulants (antithrombin, protein C, and protein S) and genetic mutations (factor V Leiden, prothrombin G20210A, etc.), play an important role in the pathogenesis of venous thrombosis. However, limited data concerning the potential contribution of these mutations to the thrombotic risk in MPNs have been provided so far. Aims: Evaluation of the prognostic value of thrombophilia markers testing in patients with JAK2 V617F positive myeloproliferative neoplasms for the choice of treatment tactics. Methods: The study included 50 patients with MPNs (diagnosed according to WHO, 2016) admitted to the National Research Center for Hematology (Moscow, Russia) for surgical assistance due to bleeding from varicose veins of the stomach and esophagus. The control group consisted of 72 donors of blood and its components. DNAs were isolated from 5-10 ml of blood or bone marrow using standard salt extraction procedure or AmpliSens reagent kit (InterLabService, Moscow, Russia). DNA concentration and purity were assessed spectrophotometrically. The JAK2 V617F mutation was quantified using the Reagent Kit from Synthol (Moscow, Russia) according to the manufacturer's instructions. In-house multiplex allele-specific real-time polymerase chain reaction (AS-PCR-RT) protocol was used to detect polymorphic alleles G1691A in the F5 gene (Leiden mutation), G20210A and T165M in the F2 gene, С677T and A1298C in the MTHFR gene, and (-675)4G/5G in the PAI-1 gene. Results:V617F JAK2 gene mutation was found in 86% of patients with MPN (group #1). In the control group (#2), no mutations in the JAK2 gene were found. The frequency distribution of mutations G1691A in the F5 gene (Leiden mutation), G20210A and T165M in the F2 gene, C677T and A1298C in the MTHFR gene, and (-675)4G/5G in the PAI-1 gene in groups #1 and #2 is presented in Table 1. In group #1, the frequency of heterozygous mutation in the F5 gene was 8.9%. This is more than 6 times higher than the similar value in group #2. The frequency of the homozygous mutation (-675)4G/5G in the PAI-1 gene in group #1 was 1.74 times higher than in group #2. The frequency of the heterozygous mutation T165M in the gene F2 in patients from group #1 and donors from group #2 were 28.9% and 4.4%, respectively. Thus, the mutation rates of the F5, F2, and PAI-1 genes are statistically significantly different between patients with MPN-associated thrombosis and donors of blood and its components. Image:Summary/Conclusion: Information about the presence of markers of hereditary thrombophilia may be of prognostic value for assessing the risk of thrombotic complications in patients with JAK2 V617F positive MPNs.